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https://www.readbyqxmd.com/read/29141223/gradients-of-rac1-nanoclusters-support-spatial-patterns-of-rac1-signaling
#1
Amanda Remorino, Simon De Beco, Fanny Cayrac, Fahima Di Federico, Gaetan Cornilleau, Alexis Gautreau, Maria Carla Parrini, Jean-Baptiste Masson, Maxime Dahan, Mathieu Coppey
Rac1 is a small RhoGTPase switch that orchestrates actin branching in space and time and protrusion/retraction cycles of the lamellipodia at the cell front during mesenchymal migration. Biosensor imaging has revealed a graded concentration of active GTP-loaded Rac1 in protruding regions of the cell. Here, using single-molecule imaging and super-resolution microscopy, we show an additional supramolecular organization of Rac1. We find that Rac1 partitions and is immobilized into nanoclusters of 50-100 molecules each...
November 14, 2017: Cell Reports
https://www.readbyqxmd.com/read/29138557/improving-intestinal-absorption-and-oral-bioavailability-of-curcumin-via-taurocholic-acid-modified-nanostructured-lipid-carriers
#2
Cihui Tian, Sajid Asghar, Yifan Wu, Zhipeng Chen, Xin Jin, Lining Yin, Lin Huang, Qineng Ping, Yanyu Xiao
The expression of multiple receptors on intestinal epithelial cells enables an actively targeted carrier to significantly enhance the oral delivery of payloads. Conjugating the receptors' ligands on the surfaces of a particulate-delivery system allows site-specific targeting. Here, we used taurocholic acid (TCA) as a ligand for uptake of nanostructured lipid carriers (NLCs) mediated by a bile-acid transporter to improve oral bioavailability of curcumin (Cur). First, synthesis of TCA-polyethylene glycol 100-monostearate (S100-TCA) was carried out...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/29133120/enhanced-oral-absorption-and-anticancer-efficacy-of-cabazitaxel-by-overcoming-intestinal-mucus-and-epithelium-barriers-using-surface-polyethylene-oxide-peo-decorated-positively-charged-polymer-lipid-hybrid-nanoparticles
#3
Tianyang Ren, Qian Wang, Ying Xu, Lin Cong, Jingxin Gou, Xiaoguang Tao, Yu Zhang, Haibing He, Tian Yin, Haotian Zhang, Yan Zhang, Xing Tang
Polymer-lipid hybrid nanoparticles, PMONPs, were developed to improve the oral absorption of cabazitaxel (CTX), a semi-synthetic taxane derivative, by overcoming multiple gastrointestinal barriers. The nano-carrier is comprised of a poly(ε-caprolactone) (PCL) and chain triglyceride (MCT) hybrid core for drug loading, and a positively charged surface while slightly concealed with a polyethylene oxide (PEO) shell by insertion of poloxamer 188, with the aim of improving the intestinal mucus permeation and epithelial cell uptake...
November 10, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/29129570/poly-vinyl-pyrrolidone-lipid-based-hybrid-nanoparticles-for-anti-viral-drug-delivery
#4
K S Joshy, S Snigdha, George Anne, Kalarikkal Nandakumar, Pothen Laly A, Thomas Sabu
Zidovudine (AZT) is an antiviral drug with moderate solubility in water. It has limited application due to its short half life in vivo and consequent requirement for frequent administrations. To solve this problem, zidovudine loaded polyvinylpyrrolidone (PVP)/stearic acid (SA)-polyethylene glycol (PEG) nanoparticles (PSNPs) were developed.The hybrid nanoparticles were prepared by emulsification-solvent evaporation method. The physico chemical characterizations of the PSNPs was done by dynamic light scattering (DLS), transmission electron microscopy (TEM), and fourier transform infra-red spectroscopy (FT-IR)...
November 9, 2017: Chemistry and Physics of Lipids
https://www.readbyqxmd.com/read/29124936/in-vivo-ct-photoacoustic-imaging-and-nir-triggered-chemo-photothermal-combined-therapy-based-on-a-gold-nanostar-mesoporous-silica-and-thermo-sensitive-liposomes-composited-nanoprobe
#5
Jie An, Xiao-Quan Yang, Kai Cheng, Xian-Lin Song, Lin Zhang, Cheng Li, Xiao-Shuai Zhang, Yang Xuan, Yuan-Yang Song, Bi-Yun Fang, Xiao-Lin Hou, Yuan-Di Zhao, Bo Liu
Safe multifunctional nanoplatforms that have multiple therapeutic functions integrated with imaging capabilities are highly desired for biomedical applications. In this paper, targeted chemo-photothermal synergistic therapy and photoacoustic/CT imaging of tumor were achieved by one novel multifunctional nanoprobe (GMS/DOX@SLB-FA), it was composed of gold nanostar core and doxorubicin (DOX) loading mesoporous silica shell (GMS), which was coated with folic acid (FA) modified thermosensitively supported lipid bilayer (FA-SLB) as gatekeeper...
November 10, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/29119867/targeted-macrophages-delivery-of-rifampicin-loaded-lipid-nanoparticles-to-improve-tuberculosis-treatment
#6
Alexandre Cc Vieira, Joana Magalhães, Sónia Rocha, Marcos S Cardoso, Susana G Santos, Margarida Borges, Marina Pinheiro, Salette Reis
AIM: This work aims to develop a mannosylated nanostructured lipid carrier (NLC) loaded with rifampicin to improve tuberculosis treatment. MATERIALS & METHODS: An active targeting strategy was used and the nanoparticles were characterized. Effects on cell viability and the antimycobacterial activity of the nanoformulations were evaluated. RESULTS: The nanoparticles developed exhibited a size of about 315 nm and polydispersity <0.2. The drug encapsulation efficiency was higher than 90% and its release was sensitive to pH...
November 9, 2017: Nanomedicine
https://www.readbyqxmd.com/read/29113042/ph-responsive-micelle-based-cytoplasmic-delivery-system-for-induction-of-cellular-immunity
#7
Eiji Yuba, Naoki Sakaguchi, Yuhei Kanda, Maiko Miyazaki, Kazunori Koiwai
(1) Background: Cytoplasmic delivery of antigens is crucial for the induction of cellular immunity, which is an important immune response for the treatment of cancer and infectious diseases. To date, fusogenic protein-incorporated liposomes and pH-responsive polymer-modified liposomes have been used to achieve cytoplasmic delivery of antigen via membrane rupture or fusion with endosomes. However, a more versatile cytoplasmic delivery system is desired for practical use. For this study, we developed pH-responsive micelles composed of dilauroyl phosphatidylcholine (DLPC) and deoxycholic acid and investigated their cytoplasmic delivery performance and immunity-inducing capability...
November 4, 2017: Vaccines
https://www.readbyqxmd.com/read/29104991/biomimetics-reconstitution-of-low-density-lipoprotein-for-targeted-drug-delivery-and-related-theranostic-applications
#8
Chunlei Zhu, Younan Xia
Low-density lipoprotein (LDL), one of the four major groups of lipoproteins for lipid transport in vivo, is emerging as an attractive carrier for the targeted delivery of theranostic agents. In contrast to the synthetic systems, LDL particles are intrinsically biocompatible and biodegradable, together with reduced immunogenicity and natural capabilities to target cancerous cells and to escape from the recognition and elimination by the reticuloendothelial system. Enticed by these attributes, a number of strategies have been developed for reconstituting LDL particles, including conjugation to the apolipoprotein, insertion into the phospholipid layer, and loading into the core...
November 6, 2017: Chemical Society Reviews
https://www.readbyqxmd.com/read/29103907/myeloid-atg16l1-does-not-affect-adipose-tissue-inflammation-or-body-mass-in-mice-fed-high-fat-diet
#9
Evelyn M S Litwinoff, Merav Y Gold, Karan Singh, Jiyuan Hu, Huilin Li, Ken Cadwell, Ann Marie Schmidt
BACKGROUND: An influx of lipid-loaded macrophages characterizes visceral adipose tissue (VAT) inflammation, which is an important factor in the development of insulin resistance (IR) in obesity. Depletion of macrophage lipids accompanies increased whole body insulin sensitivity, but the underlying mechanism is unknown. Deficiency of autophagy protein ATG16L1 is associated with increases in inflammatory diseases and lipid metabolism, but the connection between ATG16L1, IR, and obesity remains elusive...
November 2, 2017: Obesity Research & Clinical Practice
https://www.readbyqxmd.com/read/29101869/mesoporous-silica-for-drug-delivery-interactions-with-model-fluorescent-lipid-vesicles-and-live-cells
#10
Munmun Bardhan, Anupa Majumdar, Sayantan Jana, Tapas Ghosh, Uttam Pal, Snehasikta Swarnakar, Dulal Senapati
Formulated mesoporous silica nanoparticle (MSN) systems offer the best possible drug delivery system through the release of drug molecules from the accessible pores. In the present investigation, steady state and time resolved fluorescence techniques along with the fluorescence imaging were applied to investigate the interactions of dye loaded MSN with fluorescent unilamellar vesicles and live cells. Here 1,2-dimyristoyl-sn-glycero-3-phospocholine (DMPC) was used to prepare Small Unilamellar Vesicles (SUVs) as the model membrane with fluorescent 1,6-diphenyl-1,3,5-hexatriene (DPH) molecule incorporated inside the lipid bilayer...
November 1, 2017: Journal of Photochemistry and Photobiology. B, Biology
https://www.readbyqxmd.com/read/29098877/hydrophobic-binding-peptide-conjugated-hybrid-lipid-mesoporous-silica-nanoparticles-for-effective-chemo-photothermal-therapy-of-pancreatic-cancer
#11
Raj Kumar Thapa, Hanh Thuy Nguyen, Milan Gautam, Aarajana Shrestha, Eung Seok Lee, Sae Kwang Ku, Han-Gon Choi, Chul Soon Yong, Jong Oh Kim
Nanoparticle-based drug delivery systems are designed to reach tumor sites based on their enhanced permeation and retention effects. However, a lack of interaction of these nanoparticles with cancer cells might lead to reduced uptake in the tumors, which might compromise the therapeutic efficacy of the system. Therefore, we developed bortezomib and IR-820-loaded hybrid-lipid mesoporous silica nanoparticles conjugated with the hydrophobic-binding peptide, cyclosporine A (CsA), and referred to them as CLMSN/BIR...
November 2017: Drug Delivery
https://www.readbyqxmd.com/read/29096375/solid-lipid-nanoparticles-for-delivery-of-andrographolide-across-the-blood-brain-barrier-in-vitro-and-in-vivo-evaluation
#12
Giulia Graverini, Vieri Piazzini, Elisa Landucci, Daniela Pantano, Pamela Nardiello, Fiorella Casamenti, Domenico E Pellegrini-Giampietro, Anna Rita Bilia, Maria Camilla Bergonzi
Andrographolide is a major diterpenoid of Andrographis paniculata and possesses several biological activities, including protection against oxidative stress mediated neurotoxicity, inflammation-mediated neurodegeneration, and cerebral ischemia. However, this molecule shows low bioavailability, poor water solubility, and high chemical and metabolic instability. The present study reports preparation of solid lipid nanoparticles (SLN) to deliver andrographolide (AG) into the brain. SLN were prepared using Compritol 888 ATO as solid lipid and Brij 78 as surfactant and applying emulsion/evaporation/solidifying method as preparative procedure...
October 27, 2017: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/29080091/post-translational-add-ons-mark-the-path-in-exosomal-protein-sorting
#13
EDITORIAL
Olga Moreno-Gonzalo, Irene Fernandez-Delgado, Francisco Sanchez-Madrid
Extracellular vesicles (EVs) are released by cells to the extracellular environment to mediate inter-cellular communication. Proteins, lipids, nucleic acids and metabolites shuttled in these vesicles modulate specific functions in recipient cells. The enrichment of selected sets of proteins in EVs compared with global cellular levels suggests the existence of specific sorting mechanisms to specify EV loading. Diverse post-translational modifications (PTMs) of proteins participate in the loading of specific elements into EVs...
October 27, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/29078873/improving-the-efficacy-of-liposome-mediated-vascular-gene-therapy-via-lipid-surface-modifications
#14
Richard K Fisher, Samuel I Mattern-Schain, Michael D Best, Stacy S Kirkpatrick, Michael B Freeman, Oscar H Grandas, Deidra J H Mountain
BACKGROUND: We have previously defined mechanisms of intimal hyperplasia that could be targets for molecular therapeutics aimed at vascular pathology. However, biocompatible nanocarriers are needed for effective delivery. Cationic liposomes (CLPs) have been demonstrated as effective nanocarriers in vitro. However, in vivo success has been hampered by cytotoxicity. Recently, neutral PEGylated liposomes (PLPs) have been modified with cell-penetrating peptides (CPPs) to enhance cellular uptake...
November 2017: Journal of Surgical Research
https://www.readbyqxmd.com/read/29075110/polymer-lipid-hybrid-anti-her2-nanoparticles-for-targeted-salinomycin-delivery-to-her2-positive-breast-cancer-stem-cells-and-cancer-cells
#15
Jun Li, Wenqing Xu, Xiaoli Yuan, Huaiwen Chen, Hao Song, Bingquan Wang, Jun Han
PURPOSE: Breast cancer stem cells (CSCs) are responsible for the initiation, recurrence, and metastasis of breast cancer. Sufficient evidence has established that breast cancer cells can spontaneously turn into breast CSCs. Thus, it is essential to simultaneously target breast CSCs and cancer cells to maximize the efficacy of breast cancer therapy. HER2 has been found to be overexpressed in both breast CSCs and cancer cells. We developed salinomycin-loaded polymer-lipid hybrid anti-HER2 nanoparticles (Sali-NP-HER2) to target both HER2-positive breast CSCs and cancer cells...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/29068422/anticancer-effects-of-resveratrol-loaded-solid-lipid-nanoparticles-on-human-breast-cancer-cells
#16
Wenrui Wang, Lingyu Zhang, Tiantian Chen, Wen Guo, Xunxia Bao, Dandan Wang, Baihui Ren, Haifeng Wang, Yu Li, Yueyue Wang, Sulian Chen, Baoding Tang, Qingling Yang, Changjie Chen
In this study, resveratrol-loaded solid lipid nanoparticles (Res-SLNs) were successfully designed to treat MDA-MB-231 cells. The Res-SLNs were prepared using emulsification and low-temperature solidification method. The Res-SLNs were spherical, with small size, negative charge, and narrow size distribution. Compared with free resveratrol, the Res-SLNs displayed a superior ability in inhibiting the proliferation of MDA-MB-231 cells. In addition, Res-SLNs exhibited much stronger inhibitory effects on the invasion and migration of MDA-MB-231 cells...
October 25, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29068313/phosphatidylinositol-4-5-bisphosphate-optical-uncaging-potentiates-exocytosis
#17
Alexander M Walter, Rainer Müller, Bassam Tawfik, Keimpe Db Wierda, Paulo S Pinheiro, André Nadler, Anthony W McCarthy, Iwona Ziomkiewicz, Martin Kruse, Gregor Reither, Jens Rettig, Martin Lehmann, Volker Haucke, Bertil Hille, Carsten Schultz, Jakob Balslev Sorensen
Phosphatidylinositol-4,5-bisphosphate [PI(4,5)P2] is essential for exocytosis. Classical ways of manipulating PI(4,5)P2 levels are slower than metabolism, making it difficult to distinguish effects of PI(4,5)P2 from those of its metabolites. We developed a membrane-permeant, photoactivatable PI(4,5)P2, which is loaded into cells in an inactive form and activated by light, allowing sub-second increases in PI(4,5)P2 levels. By combining this compound with electrophysiological measurements in mouse adrenal chromaffin cells, we show that PI(4,5)P2 uncaging potentiates exocytosis and identify synaptotagmin-1 (the Ca(2+) sensor for exocytosis) and Munc13-2 (a vesicle priming protein) as the relevant effector proteins...
October 25, 2017: ELife
https://www.readbyqxmd.com/read/29057246/engineering-of-extracellular-vesicles-as-drug-delivery-vehicles
#18
REVIEW
Sung-Man Kim, Han-Soo Kim
Extracellular vesicles (EVs) are secreted membrane-enclosed nano-sized particles (40-1,000 nm) that deliver biological information between cells. The molecular composition of these subcellular particles includes growth factor receptors, ligands adhesion proteins, mRNA, miRNAs, lncRNA and lipids that are derived from donor cells. A number of studies demonstrated that stem cell-derived EVs are the key mediator of tissue repair and regeneration in multiple animal disease models. In addition, the composition of these particles is known to be altered in cancer and disease pathology suggesting them for useful in diagnostic and therapeutic purposes...
2017: Stem Cell Investigation
https://www.readbyqxmd.com/read/29053672/sample-extraction-and-simultaneous-chromatographic-quantitation-of-doxorubicin-and-mitomycin-c-following-drug-combination-delivery-in-nanoparticles-to-tumor-bearing-mice
#19
Rui Xue Zhang, Tian Zhang, King Chen, Ji Cheng, Paris Lai, Andrew M Rauth, K Sandy Pang, Xiao Yu Wu
Combination chemotherapy is frequently used in the clinic for cancer treatment; however, associated adverse effects to normal tissue may limit its therapeutic benefit. Nanoparticle-based drug combination has been shown to mitigate the problems encountered by free drug combination therapy. Our previous studies have shown that the combination of two anticancer drugs, doxorubicin (DOX) and mitomycin C (MMC), produced a synergistic effect against both murine and human breast cancer cells in vitro. DOX and MMC co-loaded polymer-lipid hybrid nanoparticles (DMPLN) bypassed various efflux transporter pumps that confer multidrug resistance and demonstrated enhanced efficacy in breast tumor models...
October 5, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29048372/%C3%AE-synuclein-regulates-neuronal-cholesterol-efflux
#20
Jen-Hsiang T Hsiao, Glenda M Halliday, Woojin Scott Kim
α-Synuclein is a neuronal protein that is at the center of focus in understanding the etiology of a group of neurodegenerative diseases called α-synucleinopathies, which includes Parkinson's disease (PD). Despite much research, the exact physiological function of α-synuclein is still unclear. α-Synuclein has similar biophysical properties as apolipoproteins and other lipid-binding proteins and has a high affinity for cholesterol. These properties suggest a possible role for α-synuclein as a lipid acceptor mediating cholesterol efflux (the process of removing cholesterol out of cells)...
October 19, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
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